Purging of inbreeding depression within the Irish Holstein-Friesian population

The objective of this study was to investigate whether inbreeding depression in milk production or fertility performance has been partially purged due to selection within the Irish Holstein-Friesian population. Classical, ancestral (i.e., the inbreeding of an individual's ancestors according to two different formulae) and new inbreeding coefficients (i.e., part of the classical inbreeding coefficient that is not accounted for by ancestral inbreeding) were computed for all animals. The effect of each coefficient on 305-day milk, fat and protein yield as well as calving interval, age at first calving and survival to second lactation was investigated. Ancestral inbreeding accounting for all common ancestors in the pedigree had a positive effect on 305-day milk and protein yield, increasing yields by 4.85 kg and 0.12 kg, respectively. However, ancestral inbreeding accounting only for those common ancestors, which contribute to the classical inbreeding coefficient had a negative effect on all milk production traits decreasing 305-day milk, fat and protein yields by -8.85 kg, -0.53 kg and -0.33 kg, respectively. Classical, ancestral and new inbreeding generally had a detrimental effect on fertility and survival traits. From this study, it appears that Irish Holstein-Friesians have purged some of their genetic load for milk production through many years of selection based on production alone, while fertility, which has been less intensely selected for in the population demonstrates no evidence of purging

Epistasis in a Model of Molecular Signal Transduction

Biological functions typically involve complex interacting molecular networks, with numerous feedback and regulation loops. How the properties of the system are affected when one, or several of its parts are modified is a question of fundamental interest, with numerous implications for the way we study and understand biological processes and treat diseases. This question can be rephrased in terms of relating genotypes to phenotypes: to what extent does the effect of a genetic variation at one locus depend on genetic variation at all other loci? Systematic quantitative measurements of epistasis – the deviation from additivity in the effect of alleles at different loci – on a given quantitative trait remain a major challenge. Here, we take a complementary approach of studying theoretically the effect of varying multiple parameters in a validated model of molecular signal transduction. To connect with the genotype/phenotype mapping we interpret parameters of the model as different loci with discrete choices of these parameters as alleles, which allows us to systematically examine the dependence of the signaling output – a quantitative trait – on the set of possible allelic combinations. We show quite generally that quantitative traits behave approximately additively (weak epistasis) when alleles correspond to small changes of parameters; epistasis appears as a result of large differences between alleles. When epistasis is relatively strong, it is concentrated in a sparse subset of loci and in low order (e.g. pair-wise) interactions. We find that focusing on interaction between loci that exhibit strong additive effects is an efficient way of identifying most of the epistasis. Our model study defines a theoretical framework for interpretation of experimental data and provides statistical predictions for the structure of genetic interaction expected for moderately complex biological circuits

Dissecting Genetic Networks Underlying Complex Phenotypes: The Theoretical Framework

Great progress has been made in genetic dissection of quantitative trait variation during the past two decades, but many studies still reveal only a small fraction of quantitative trait loci (QTLs), and epistasis remains elusive. We integrate contemporary knowledge of signal transduction pathways with principles of quantitative and population genetics to characterize genetic networks underlying complex traits, using a model founded upon one-way functional dependency of downstream genes on upstream regulators (the principle of hierarchy) and mutual functional dependency among related genes (functional genetic units, FGU). Both simulated and real data suggest that complementary epistasis contributes greatly to quantitative trait variation, and obscures the phenotypic effects of many ‘downstream’ loci in pathways. The mathematical relationships between the main effects and epistatic effects of genes acting at different levels of signaling pathways were established using the quantitative and population genetic parameters. Both loss of function and “co-adapted” gene complexes formed by multiple alleles with differentiated functions (effects) are predicted to be frequent types of allelic diversity at loci that contribute to the genetic variation of complex traits in populations. Downstream FGUs appear to be more vulnerable to loss of function than their upstream regulators, but this vulnerability is apparently compensated by different FGUs of similar functions. Other predictions from the model may account for puzzling results regarding responses to selection, genotype by environment interaction, and the genetic basis of heterosis

Genetic variation of male reproductive success in a laboratory population of Anopheles gambiae

<p>Abstract</p> <p>Background</p> <p>For Anopheline mosquitoes, the vectors of human malaria, genetic variation in male reproductive success can have important consequences for any control strategy based on the release of transgenic or sterile males.</p> <p>Methods</p> <p>A quantitative genetics approach was used to test whether there was a genetic component to variation in male reproductive success in a laboratory population of <it>Anopheles gambiae</it>. Swarms of full sibling brothers were mated with a fixed number of females and their reproductive success was measured as (1) proportion of ovipositing females, (2) proportion of ovipositing females that produced larvae, (3) proportion of females that produced larvae, (4) number of eggs laid per female, (5) number of larvae per ovipositing female and (6) number of larvae per female.</p> <p>Results</p> <p>The proportion of ovipositing females (trait 1) and the proportion of ovipositing females that produced larvae (trait 2) differed among full sib families, suggesting a genetic basis of mating success. In contrast, the other measures of male reproductive success showed little variation due to the full sib families, as their variation are probably mostly due to differences among females. While age at emergence and wing length of the males were also heritable, they were not associated with reproductive success. Larger females produced more eggs, but males did not prefer such partners.</p> <p>Conclusion</p> <p>The first study to quantify genetic variation for male reproductive success in <it>A. gambiae </it>found that while the initial stages of male reproduction (i.e. the proportion of ovipositing females and the proportion of ovipositing females that produced larvae) had a genetic basis, the overall reproductive success (i.e. the mean number of larvae per female) did not.</p

Sex Differences in Sand Lizard Telomere Inheritance: Paternal Epigenetic Effects Increases Telomere Heritability and Offspring Survival

To date, the only estimate of the heritability of telomere length in wild populations comes from humans. Thus, there is a need for analysis of natural populations with respect to how telomeres evolve.Here, we show that telomere length is heritable in free-ranging sand lizards, Lacerta agilis. More importantly, heritability estimates analysed within, and contrasted between, the sexes are markedly different; son-sire heritability is much higher relative to daughter-dam heritability. We assess the effect of paternal age on Telomere Length (TL) and show that in this species, paternal age at conception is the best predictor of TL in sons. Neither paternal age per se at blood sampling for telomere screening, nor corresponding age in sons impact TL in sons. Processes maintaining telomere length are also associated with negative fitness effects, most notably by increasing the risk of cancer and show variation across different categories of individuals (e.g. males vs. females). We therefore tested whether TL influences offspring survival in their first year of life. Indeed such effects were present and independent of sex-biased offspring mortality and offspring malformations.TL show differences in sex-specific heritability with implications for differences between the sexes with respect to ongoing telomere selection. Paternal age influences the length of telomeres in sons and longer telomeres enhance offspring survival

Genetic Networks Controlling Structural Outcome of Glucosinolate Activation across Development

Most phenotypic variation present in natural populations is under polygenic control, largely determined by genetic variation at quantitative trait loci (QTLs). These genetic loci frequently interact with the environment, development, and each other, yet the importance of these interactions on the underlying genetic architecture of quantitative traits is not well characterized. To better study how epistasis and development may influence quantitative traits, we studied genetic variation in Arabidopsis glucosinolate activation using the moderately sized Bayreuth×Shahdara recombinant inbred population, in terms of number of lines. We identified QTLs for glucosinolate activation at three different developmental stages. Numerous QTLs showed developmental dependency, as well as a large epistatic network, centered on the previously cloned large-effect glucosinolate activation QTL, ESP. Analysis of Heterogeneous Inbred Families validated seven loci and all of the QTL×DPG (days post-germination) interactions tested, but was complicated by the extensive epistasis. A comparison of transcript accumulation data within 211 of these RILs showed an extensive overlap of gene expression QTLs for structural specifiers and their homologs with the identified glucosinolate activation loci. Finally, we were able to show that two of the QTLs are the result of whole-genome duplications of a glucosinolate activation gene cluster. These data reveal complex age-dependent regulation of structural outcomes and suggest that transcriptional regulation is associated with a significant portion of the underlying ontogenic variation and epistatic interactions in glucosinolate activation

Invasive Plants and Enemy Release: Evolution of Trait Means and Trait Correlations in Ulex europaeus

Several hypotheses that attempt to explain invasive processes are based on the fact that plants have been introduced without their natural enemies. Among them, the EICA (Evolution of Increased Competitive Ability) hypothesis is the most influential. It states that, due to enemy release, exotic plants evolve a shift in resource allocation from defence to reproduction or growth. In the native range of the invasive species Ulex europaeus, traits involved in reproduction and growth have been shown to be highly variable and genetically correlated. Thus, in order to explore the joint evolution of life history traits and susceptibility to seed predation in this species, we investigated changes in both trait means and trait correlations. To do so, we compared plants from native and invaded regions grown in a common garden. According to the expectations of the EICA hypothesis, we observed an increase in seedling height. However, there was little change in other trait means. By contrast, correlations exhibited a clear pattern: the correlations between life history traits and infestation rate by seed predators were always weaker in the invaded range than in the native range. In U. europaeus, the role of enemy release in shaping life history traits thus appeared to imply trait correlations rather than trait means. In the invaded regions studied, the correlations involving infestation rates and key life history traits such as flowering phenology, growth and pod density were reduced, enabling more independent evolution of these key traits and potentially facilitating local adaptation to a wide range of environments. These results led us to hypothesise that a relaxation of genetic correlations may be implied in the expansion of invasive species

Tandemly repeated DNA families in the mouse genome

<p>Abstract</p> <p>Background</p> <p>Functional and morphological studies of tandem DNA repeats, that combine high portion of most genomes, are mostly limited due to the incomplete characterization of these genome elements. We report here a genome wide analysis of the large tandem repeats (TR) found in the mouse genome assemblies.</p> <p>Results</p> <p>Using a bioinformatics approach, we identified large TR with array size more than 3 kb in two mouse whole genome shotgun (WGS) assemblies. Large TR were classified based on sequence similarity, chromosome position, monomer length, array variability, and GC content; we identified four superfamilies, eight families, and 62 subfamilies - including 60 not previously described. 1) The superfamily of centromeric minor satellite is only found in the unassembled part of the reference genome. 2) The pericentromeric major satellite is the most abundant superfamily and reveals high order repeat structure. 3) Transposable elements related superfamily contains two families. 4) The superfamily of heterogeneous tandem repeats includes four families. One family is found only in the WGS, while two families represent tandem repeats with either single or multi locus location. Despite multi locus location, TRPC-21A-MM is placed into a separated family due to its abundance, strictly pericentromeric location, and resemblance to big human satellites.</p> <p>To confirm our data, we next performed <it>in situ </it>hybridization with three repeats from distinct families. TRPC-21A-MM probe hybridized to chromosomes 3 and 17, multi locus TR-22A-MM probe hybridized to ten chromosomes, and single locus TR-54B-MM probe hybridized with the long loops that emerge from chromosome ends. In addition to <it>in silico </it>predicted several extra-chromosomes were positive for TR by <it>in situ </it>analysis, potentially indicating inaccurate genome assembly of the heterochromatic genome regions.</p> <p>Conclusions</p> <p>Chromosome-specific TR had been predicted for mouse but no reliable cytogenetic probes were available before. We report new analysis that identified <it>in silico </it>and confirmed <it>in situ </it>3/17 chromosome-specific probe TRPC-21-MM. Thus, the new classification had proven to be useful tool for continuation of genome study, while annotated TR can be the valuable source of cytogenetic probes for chromosome recognition.</p

Recreational and occupational field exposure to freshwater cyanobacteria – a review of anecdotal and case reports, epidemiological studies and the challenges for epidemiologic assessment

Cyanobacteria are common inhabitants of freshwater lakes and reservoirs throughout the world. Under favourable conditions, certain cyanobacteria can dominate the phytoplankton within a waterbody and form nuisance blooms. Case reports and anecdotal references dating from 1949 describe a range of illnesses associated with recreational exposure to cyanobacteria: hay fever-like symptoms, pruritic skin rashes and gastro-intestinal symptoms are most frequently reported. Some papers give convincing descriptions of allergic reactions while others describe more serious acute illnesses, with symptoms such as severe headache, pneumonia, fever, myalgia, vertigo and blistering in the mouth. A coroner in the United States found that a teenage boy died as a result of accidentally ingesting a neurotoxic cyanotoxin from a golf course pond. This death is the first recorded human fatality attributed to recreational exposure to cyanobacteria, although uncertainties surround the forensic identification of the suspected cyanotoxin in this case. We systematically reviewed the literature on recreational exposure to freshwater cyanobacteria. Epidemiological data are limited, with six studies conducted since 1990. Statistically significant increases in symptoms were reported in individuals exposed to cyanobacteria compared to unexposed counterparts in two Australian cohort studies, though minor morbidity appeared to be the main finding. The four other small studies (three from the UK, one Australian) did not report any significant association. However, the potential for serious injury or death remains, as freshwater cyanobacteria under bloom conditions are capable of producing potent toxins that cause specific and severe dysfunction to hepatic or central nervous systems. The exposure route for these toxins is oral, from ingestion of recreational water, and possibly by inhalation. A range of freshwater microbial agents may cause acute conditions that present with features that resemble illnesses attributed to contact with cyanobacteria and, conversely, acute illness resulting from exposure to cyanobacteria or cyanotoxins in recreational waters could be misdiagnosed. Accurately assessing exposure to cyanobacteria in recreational waters is difficult and unreliable at present, as specific biomarkers are unavailable. However, diagnosis of cyanobacteria-related illness should be considered for individuals presenting with acute illness following freshwater contact if a description is given of a waterbody visibly affected by planktonic mass development